LIM kinase 1 deficient mice have reduced bone mass

The cytoskeleton determines cell shape and is involved in cell motility. It also plays a role in differentiation and in modulating specialized cellular functions. LIM kinase 1 (LIMK1) participates in cytoskeletal remodeling by phosphorylating and inactivating the actin-severing protein, cofilin. Severing F-actin to release G-actin monomers is required for actin cytoskeletal remodeling. Although less well established, LIMK1 may also influence the cell cycle and modulate metalloproteinase activity. Since the role of LIMK1 in bone cell biology has not been reported, the skeletal phenotype of LIMK1^?/? mice was examined. LIMK1^?/? mice had significantly reduced trabecular bone mass when analyzed by microCT (p < 0.01). Histomorphometric analyses demonstrated a 31% reduction in the number of osteoblasts (p = 0.0003) and a 23% reduction in osteoid surface (p = 0.0005). The number of osteoclasts was no different in control and knock out animals. Consistent with the in vivo findings in osteoblasts, the number of osteoblast colony forming units in LIMK1^?/? bone marrow was reduced by nearly 50%. Further, osteoblasts isolated from LIMK1^?/? mice showed significantly reduced rates of mineralization in vitro. Osteoclasts from LIMK1^?/? mice evidenced more rapid cytoskeletal remodeling in response to treatment with CSF1. In keeping with this latter finding, basal levels of phospho-cofilin were reduced in LIMK1^?/? osteoclasts. LIMK1^?/? osteoclasts also resorbed dentine slices to a greater extent in vitro and were more active in a pit assay. These data support the hypothesis that LIMK1 is required for normal osteoblast differentiation. In addition, its absence leads to increased cytoskeletal remodeling and bone resorption in osteoclasts.     

Homeostatic cytokines and expansion of regulatory T cells accompany thymic impairment in children with Down syndrome

Down syndrome (DS), the most common chromosomal abnormality in humans, is characterized by precocious immunologic aging that results, among other things, in alterations of B and T lymphocyte subsets and natural killer cells, defective phagocytosis, and chemotaxis of polymorphonuclear leukocytes. We studied 30 children affected by DS, compared them to 29 healthy controls, and evaluated the functionality of the thymus (by measuring the amount of lymphocytes that express the signal-joint T cell receptor rearrangement excision circles [sj-TREC+]), the plasma levels of interleukin (IL)-7 and IL-15, the proliferative T cell response to these cytokines, the expression of the alpha chain of the IL-7 receptor (CD127), the extrathymic differentiation of T lymphocytes, and the presence of natural regulatory T cells (Tregs) in peripheral blood. We found that DS children had a significantly lower number of sj-TREC+ lymphocytes, the levels of which were strongly correlated with age. We found higher plasma levels of IL-7 and IL-15 than in healthy controls, and a higher proliferative T cell response to IL-15. DS children also showed a lower percentage of CD4(+) cells and profound alterations of T cell differentiation, along with increased amount of Tregs and of cells expressing markers of apoptosis. We can thus hypothesize that the precocious thymic involution occurring in DS is mirrored by a high production of IL-7 and IL-15, which is crucial for cell survival and proliferation. The complex alterations present in the periphery are likely the result of a compensatory mechanism: the overproduction of homeostatic cytokines could be a reaction to the impaired intrathymic production of T lymphocytes and/or to the expansion of Treg in the periphery, and could be required to allow the survival of T cells.     

Oral candidosis and the therapeutic use of antifungal agents in dentistry

This paper reviews the current concepts of mycology and candidal infections as they relate to the oral cavity. Proposed classification for the presentation of oral candidosis is outlined as are examples of these topical infections, such as erythematous, pseudo-membranous and hyperplastic candidosis, as well as angular chelitis and median rhomboid glossitis. The diagnosis and principles of management of oral candidosis are discussed, the therapeutic agents available for the management of these infections are presented and a treatment protocol for the management of patients with oral candidosis is given.     

Immediate occlusal loading of Osseotite implants in the lower edentulous jaw. A multicenter prospective study

OBJECTIVE: This paper reports the results of a prospective multicenter clinical study on immediately fully occlusally loaded full-arch screw-retained prostheses with distal extensions (hybrid prostheses) supported by Osseotite implants inserted in edentulous lower jaws. METHOD AND MATERIAL: Sixty-two patients were enrolled in four clinical centers. Three hundred and twenty-five Osseotite implants were inserted and occlusally loaded according to an immediate loading protocol. The temporary prosthesis was delivered 4 h from surgery. The final prosthesis was delivered after 6 months. Marginal bone loss was monitored from periapical radiographs using a computerized technique. RESULTS: Two implants failed to integrate within 2 months of occlusal loading. A cumulative implant success rate of 99.4% was achieved for a period of 12-60 months postplacement (mean 28.6+/-14.1 (SD) months). Crestal bone loss around the immediately loaded implants was similar to that reported for standard delayed loading protocols. CONCLUSION: The results of this study suggest that the rehabilitation of the edentulous mandible by an immediate occlusally loaded hybrid prosthesis supported by five to six Osseotite implants represents a viable alternative treatment to classic delayed loading protocols.     

Laparoscopic liver resection for benign and malignant liver tumors

BACKGROUND:Laparoscopic liver resection is one of the most complex procedures in hepatobiliary surgery.In the last two decades,laparoscopic liver surgery has emerged as an option at major academic institutions.The purpose of this study is to describe the initial experience of minimally invasive liver resections at a non-academic institution. METHODS:We retrospectively reviewed medical records of patients undergoing laparoscopic liver resections between June 2006 and December 2009 at our center.Indications, ...     

Dopamine transporter PET in normal aging: Dopamine transporter decline and its possible role in preservation of motor function

Objectives : To determine the impact of age‐related decline in dopamine transporter (DAT) expression on motor function in the elderly. Methods : About 33 normal individuals of a wide age range were scanned with PET employing d‐threo‐[¹¹C]‐methylphenidate (MP, a marker of DAT) and [¹¹C]‐dihydrotetrabenazine (DTBZ, that binds to the vesicular monoamine transporter Type 2). Motor function was assessed using the Purdue Pegboard Test (PPB). We analyzed the relationship between [¹¹C]‐MP and motor performance. Results : Age ranged from 27‐ to 77‐year old (mean ± SD, 54.75 ± 14.14). There was no age‐related decline in binding potentials (BP) for [¹¹C]‐DTBZ. In contrast, [¹¹C]‐MP BP was inversely related to age in all striatal regions analyzed (caudate: reduction of 11.2% per decade, P < 0.0001, r = ?0.86; putamen: reduction of 10.5% per decade, P < 0.0001, r = ?0.80). A differential effect of [¹¹C]‐MP on PPB could be observed according to age group. There was a positive relation between the PPB and [¹¹C]‐MP in young individuals (coefficient = 13.56), whereas in individuals greater than 57 years this relationship was negative (coefficient = ?19.53, P = 0.031). Conclusions : Our findings confirm prior observations of age‐related DAT decline and suggest that this phenomenon is independent of changes in VMAT2. After the fifth decade of life, this reduction in DAT binding is associated with a motor performance comparable to mid‐adult life. These findings imply that biochemical processes associated with healthy aging may offset the naturaldecline in motor function observed in the elderly. Synapse 64:146–151, 2010. © 2009 Wiley‐Liss, Inc.     

The novel HLA-C*06:58 allele, identified by sequence-based typing in an Italian family

The novel HLA-C allele C*06:58 shows one nucleotide change from C*06:02:01:01 at nt 366 from G to A, resulting in an amino acid change at codon 98 of exon 3 from Met to Ile.